Induced pluripotent stem (iPS) cells can be produced from somatic cells by introducing Oct3/4, Sox2, Klf4, and c-Myc (Non-patent Document 1, Patent Document 1). This can be achieved by reprogramming the parent somatic cell transcription network and epigenetic signatures. iPS cells bring various benefits for basic research, drug innovation, and regenerative medicine. However, it is still a serious problem that cell populations of produced iPS cells are more heterogeneous in quality than cell populations of embryonic-stem cells (ES cells). For example, while ES cells have small variance in property among cells and substantially any cell can be differentiated into the intended cell, iPS cells have large variance in property among cells and there have often been cells that cannot been differentiated into the intended cell. It is important for basic studies and the clinical purpose that any iPS cell displays high quality without variance.
Many attempts have been made to solve the problem that cell populations of iPS cells are heterogeneous in quality. For example, Patent Document 2 discloses that the production efficiency and stability of iPS cells can be improved by the predetermined number of times of introduction of a predetermined amount of an Oct3/4 gene, a Klf4 gene, a c-Myc gene, and a Sox2 gene into somatic cells. Moreover, Patent Document 3 discloses that induced pluripotent stem cells (iPS cells) excellent in quality can be produced efficiently in a short period of time by introducing into somatic cells a Prdm14 gene or a gene product thereof, an Esrrb gene or a gene product thereof, and a Sall4a gene or a gene product thereof, in addition to an Oct3/4 gene or a gene product thereof, a Sox2 gene or a gene product thereof, a Klf4 gene or a gene product thereof, and a c-Myc gene or a gene product thereof. Furthermore, Patent Document 4 discloses that induced pluripotent stem cells (iPS cells) excellent in quality can be produced efficiently in a short period of time by introducing into somatic cells a Jarid2 mutant gene or a gene product thereof in addition to an Oct3/4 gene or a gene product thereof, a Sox2 gene or a gene product thereof, a Klf4 gene or a gene product thereof, and a c-Myc gene or a gene product thereof. However, there has been still room for improvement in quality of iPS cells. Therefore, the development of a method for producing high-quality iPS cells with smaller variance in quality has been demanded.
The linker histone H1 family binds to linker DNA and generates higher-order chromatin structures to control gene expression. The members of the linker histone H1 family include histones H1a, H1b, H1c, H1d, H1e, H1foo, H1x, H1.0, H1t, H1T2, and HILS1. Most members of the linker histone family are somatic linker histones that condense chromatin. Accordingly, such structures generally repress general gene transcription activity (Non-patent Documents 2 and 3).